Summary

This was the UK's own test of puberty blockers, run by the Tavistock's gender clinic for children from 2011. Forty-four carefully chosen 12–15-year-olds were given a blocker drug and followed until they were over 16. The blockers paused puberty as intended. But there was no measurable change in emotional distress, self-harm, quality of life or gender distress, and bone density fell behind other teens their age. Most young people spoke positively about the treatment in interviews, and 43 of 44 went on to cross-sex hormones. The authors call for larger studies. There was no comparison group, numbers fell sharply after the first year, and a later re-analysis found up to a third got worse. So the study offers no evidence that blockers help mental health.

Key findings

• 重い長引く性別への苦痛のある12～15歳の若者44人（男性として生まれた25人、女性として生まれた19人）が、クリニックでの典型的には2年の評価の後、2011年から2015年の間に思春期ブロッカーを開始しました。
• 1年、2年、3年後のいずれでも、親も若者本人も、情緒や行動の問題、自傷に変化があったとは報告しませんでした。
• 生活の質、自分の体についての気持ち、性別への苦痛、そして（臨床医が判断した）対処の度合いも、ほとんど変化しませんでした。著者らは、ブロッカーが体を望む性の方向に変えるわけではないと述べています。
• 腰の骨密度は他の10代よりゆっくりしか増加せず、年齢に比べて遅れをとり、身長の伸びも遅くなりました。
• 頭痛、ほてり、疲労感などの予想される副作用は多く見られ、15～24か月後の聞き取りでは38%が元気がないと答えました。
• 44人中43人（98%）が異性ホルモンに進み、ブロッカーの後にやめる人はほとんどいないというオランダの知見と一致していました。
• 2年後にデータに残っていた若者は24人だけ、3年後には14人（自分で質問票に記入したのは3年後に6人だけ）だったため、長期的な影響についてはほとんど言えません。
• McPhersonとFreedmanによる同じデータの2024年の再分析では、指標、時点、報告者によって、15～34%の若者が明らかに悪化していることが分かりました。

Abstract

BACKGROUND: In adolescents with severe and persistent gender dysphoria (GD), gonadotropin releasing hormone analogues (GnRHa) are used from early/middle puberty with the aim of delaying irreversible and unwanted pubertal body changes. Evidence of outcomes of pubertal suppression in GD is limited. METHODS: We undertook an uncontrolled prospective observational study of GnRHa as monotherapy in 44 12-15 year olds with persistent and severe GD. Prespecified analyses were limited to key outcomes: bone mineral content (BMC) and bone mineral density (BMD); Child Behaviour CheckList (CBCL) total t-score; Youth Self-Report (YSR) total t-score; CBCL and YSR self-harm indices; at 12, 24 and 36 months. Semistructured interviews were conducted on GnRHa. RESULTS: 44 patients had data at 12 months follow-up, 24 at 24 months and 14 at 36 months. All had normal karyotype and endocrinology consistent with birth-registered sex. All achieved suppression of gonadotropins by 6 months. At the end of the study one ceased GnRHa and 43 (98%) elected to start cross-sex hormones. There was no change from baseline in spine BMD at 12 months nor in hip BMD at 24 and 36 months, but at 24 months lumbar spine BMC and BMD were higher than at baseline (BMC +6.0 (95% CI: 4.0, 7.9); BMD +0.05 (0.03, 0.07)). There were no changes from baseline to 12 or 24 months in CBCL or YSR total t-scores or for CBCL or YSR self-harm indices, nor for CBCL total t-score or self-harm index at 36 months. Most participants reported positive or a mixture of positive and negative life changes on GnRHa. Anticipated adverse events were common. CONCLUSIONS: Overall patient experience of changes on GnRHa treatment was positive. We identified no changes in psychological function. Changes in BMD were consistent with suppression of growth. Larger and longer-term prospective studies using a range of designs are needed to more fully quantify the benefits and harms of pubertal suppression in GD.

Conclusion

Treatment with GnRHa was efficacious in suppressing pubertal progression; anticipated effects of sex-hormone withdrawal were common and there were no unexpected adverse events. BMD increased in the lumbar spine and was stable at the hip, while BMD z-scores fell, consistent with delayed puberty. Overall participant experience was positive, but the authors identified no changes in psychological function, quality of life or degree of gender dysphoria. The great majority went on to cross-sex hormones; one did not, which the authors took as evidence that gender identity development continues on GnRHa. Larger, longer-term studies using a range of designs are needed to quantify benefits and harms.